1. Field of the Invention
This invention relates to a new tripeptide having an amino acid sequence L-lysyl-glycyl-L-histidine and/or metal complexes thereof, and a pharmaceutical composition for wound healing containing the same as an active ingredient.
2. Description of the Prior Art
Various growth factors are known to be involved in the process of wound healing (Dijke et al., Biotechnology, Vol. 7, p. 793-798, 1989). TGF-.beta. (transforming growth factor-.beta.) and PDGF (platelet-derived growth factor), in particular, are known to proliferate fibroblasts, induce the cells to a damaged site and enhance wound repairing.
Some tripeptides and metal complexes thereof have been known to have a cell proliferation effect. For example, glycyl-L-histidyl-L-lysine, which was isolated from plasma or synthesized and metal complexes thereof, such as, glycyl-L-histidyl-L-lysine: copper (II) are involved in cell proliferation of hepatocytes, neurocytes, kidney cells, thyroid cells, etc., and maintenance of growth (Picart, L. Method, Enzym. Vol. 147, p. 314-328, 1987; Picart, L. IN Vitro, Vol. 17, p. 459-466, 1981; Picart, L. U.S. Pat. No. 4,760,051 ). It is assumed that the cell proliferation activity of glycyl-L-histidyl-L-lysine involves binding of an essential metal ion of trace elements such as copper ion and incorporating the copper ion in cells (Picart, L. IN Vitro, Vol. 17, p. 459-466, 1981). Also disclosed is a use of glycyl-L-histidyl-L-lysine and metal complexes thereof, for example, glycyl-L-histidyl-L-lysine: copper (II) as an agent for promoting a therapy of affected bones and other hard tissues such as cartilage of warm-blooded animals (Picart, L. R., Japanese Patent Publication No. Hei 5-501253).
L-lysil-L-histidyl-glycine was isolated from an avian bursa fabricii as a B cell differentiating hormone (Audhya, T. et al. Science Vol. 231, p. 997-999, 1986). Also it is disclosed that L-lysyl-L-histidyl-glycine is used as an agent for promoting a therapy for the affected bones and other hard tissues such as cartilage (Picart, L. R., the above-mentioned Patent Publication).
L-histidyl-glycyl-L-lysine and L-histidyl-L-lysyl-glycine have been isolated from the feline spinal marrow as an inhibitor of transmission of neurocytes (Lore, C. J. et al., Nature, Vol. 264, p. 188-189, 1976). On the other hand, only glycyl-L-histidyl-lysine is known to constitute a metal complex with a metal ion, for example, copper ion among the above-mentioned tripeptides (Picart, L., the afore-mentioned).
However, it has never been reported that L-lysyl-glycyl-L-histidine nor metal complexes thereof, for example, L-lysyl-glycyl-L-histidine copper (II) proliferates fibroblasts or is effective for wound healing.